The present invention relates to a container which is suitable for an analysis inspection which requires a high quantitative accuracy. More particularly the present invention relates to the container by which all of the quantity of a specimen in the container can be substantially completely aspirated with being disposed a front end portion of a pipette tip in contact with a surface of the inside bottom of the container. Moreover, the present invention relates to the container which can largely enhance an efficiency of agitating by uniforming a diffusion of the specimen on the occasion of discharging it.
In order to maintain a precision of an analysis in a high level, as is well-known, a quantitative precision by a pipette device must be exactly maintained. In case of a conventional container, an inside bottom part of the container is formed so as to have a plane surface or a vertical sectional shape being semicircle or substantially U-like. Therefore, aspirating or discharging a sample and/or a reagent can not be executed in a state that a front end part of a pipette tip remains to be disposed in contact with the inside bottom part of the container. As a result, aspirating or discharging a sample and a reagent can be executed in a situation that the front end part of the pipette tip is kept to be lifted from the inside bottom part of the container slightly. Consequently, a small amount of samples and reagents always remains behind the container. In order to compensate this remaining amount, more amount than the actually necessary amount of aspirating needs be aspirated and/or discharged by the pipette tip. Thus, it is inevitable that samples or reagents being not aspirated remain behind the container. As a result, it has a problem that a high quantitative analysis can not be executed.
A conventional means to solve such a problem is shown in FIG. 16 for example. A front end part 2 of a pipette tip 1 is cut diagonally in order to be able to aspirate and discharge a sample S in a state that the front end part 2 of the pipette tip 1 is disposed in contact with an inside bottom part 4 of a container 3. Also, as shown in FIG. 18, another conventional means in which has one or more caves 5 are mounted in the front end part of the pipette tip 1, is proposed. It is designed so that an opening of the pipette tip 1 can not be blockaded by the contact with the inside bottom part 4 of the container 3.
But, even if the front end part 2 of the pipette tip 1 is cut diagonally, the liquid below a level W in FIG. 16 slightly lower than an upper rim of the opening of the front end part which is cut diagonally, can not be completely aspirated. As shown in FIG. 17, when the aspirated samples and/or reagents are discharged in the container 3, those in the one side of the container 3 are agitated by the pressure of discharging. But, the other side of container 3 which does not face the above-mentioned opening cut diagonally, is not directly affected by the pressure of discharging. Therefore, the conventional means has a problem that the agitating efficiency on the opposite side of the opening is low and it is difficult to get a uniform agitating effect, i.e. a uniform state of reaction. Also, it has a problem that manufacture of the pipette tip is not easier and a cost of manufacture increases.
In the same way, the conventional means which is bored by caves 5 in the front end part of the pipette tip 1, cannot aspirate a liquid S below the position where the caves 5 are bored, too. Also, when the aspirated liquid is discharged, the liquid is discharged only in the direction of the opening of the caves 5. Therefore, the conventional means has the problem that it is difficult to get a uniform agitating effect. Moreover, as the manufacturing step to bore one or more caves 5 is necessary, the conventional means has a problem that the manufacture of pipette tip 1 is complicated and a manufacture cost increases.
When liquid is aspirated and discharged in a state that the front end part of the pipette tip is kept to be lifted from the surface of the bottom part of the container, samples or reagents are tend to stick to the outside surface of the pipette tip. Therefore, the conventional means has a problem that a concentration of a sample is changed by samples or reagents being stuck and has a problem that the conventional means is difficult to get high precision results.
The present invention has been accomplished under these circumstances and has the following objects.
It is a first object of the present invention to provide a container which can solve the above problems of the conventional arts by improvement.
It is a second object of the present invention to provide a container which enables the pipette means to execute a reliable step of dispensing and/or agitating by constituting so as to be able to aspirate and/or discharge in a predetermined quantity without blockading a front end part of a liquid sucking/discharging line, on the occasion of the aspirating and/or discharging samples and/or reagents in the container.
It is a third object of the present invention to provide a container which can realize a high precision inspection of all of the quantity by being able to aspirate all of the quantity in the container, and to treat all of the quantity as being fixed without necessity of the surplus of the samples and/or reagents.
It is a fourth object of the present invention to provide a container which can realize reducing a necessary space by accumulating vessels mounted in the container in a high density and moreover by providing the optimal containers for each process, and can realize the efficient process by reducing a transferring distance of the contents of the container, by a quick and prompt operation, and by saving energy.
It is a fifth object of the present invention to provide a container which has a simple structure, and is easy and inexpensive to manufacture by accumulating vessels in a high density.
It is a sixth object of the present invention to provide a container which can realize a prompt and efficient treatment by providing vessels having various capacity for treating, measuring and holding pipette tip, being necessary to the series of the process within a container.
It is a seventh object of the present invention to provide a container which can be so reliable as preventing from cross-contamination surely.
It is an eighth object of the present invention to provide a container which is suitable to attempt to automate a series of process and to exclude the participation of the operation of human being from beginning to end as much as possible.
It is a ninth object of the present invention to provide a container which can reduce a mechanical driving movement being necessary for the process from beginning to end and can realize such a container that the number of the moving parts for the process are reduced.
To achieve these objects, the container according to the first aspect of the present invention comprises a gap part formed near a center of an inside bottom part of the container to have a smaller width than a caliber of a front end portion of a liquid sucking/discharging line adapted to be inserted in the container and pulled out of the container, and a uniformly falling slope extending from an inside wall of the container toward a border of the gap part, wherein the gap part to have a shape being capable of aspirating and discharging all of the quantity of liquid through the front end portion even in a state that the front end portion is disposed in contact with the inside bottom part.
Thus, the reliable dispensing and/or agitating step by a pipette device can be realized by constituting so as to be able to aspirate and/or discharge a predetermined amount without blockading the front end portion of the liquid sucking/discharging line when the samples and/or reagents in container are aspirated and/or discharged. Moreover, as the present invention can aspirate all of the quantity in the container, a surplus of samples or reagents are not necessary to compensate the remaining amount. As the present invention can treat all of the quantity as being a fixed, the present invention can realize a high precision inspection of all of the quantity. Furthermore, the container can be inexpensively provided because of the simple structure.
A second aspect of the present invention is that, in the first aspect, the gap part comprises a ditch or ditches having a longer size than the caliber of the front end portion of the liquid sucking/discharging line, and being formed to be substantially concave in a vertical section. Though the depth of the ditch or ditches is not restricted to a particular size, it is preferable that the depth is determined to be so shallow as to achieve aspirating all of the quantity. The present aspect of the invention can be more effective than the first aspect of the invention in regard to the uniforomity of agitating.
A third aspect of the present invention is that, in the second aspect, the plural ditches are arranged so as to be radiated. The xe2x80x9cradiatedxe2x80x9d arrangement includes asterisk, cross and three-forked road arrangement et al.
A fourth aspect of the present invention is that, in the first aspect, the gap part is formed so as to have plural concavities or convexities having a smaller size than the caliber of the front end portion of the liquid sucking/discharging line.
A fifth aspect of the present invention is that, in the first to fourth aspect, the gap part is formed so as to have a falling slope extending towards the center of the inside bottom part of a main body of the container. By this aspect of the invention, substantially all of the quantity in container can be aspirated surely.
A sixth aspect of the present invention is that, in the first to fifth aspect, plural vessels for storing liquid and so on are arranged along a line or lines so as to form a cartridge container or a microplate.
This aspect of the invention can realize narrowing a necessary space by accumulating the vessels in a high density and can realize the efficient treatment by shortening a transferring distance of the contents in vessels, by a quick and prompt operation, and by saving energy. Furthermore, a container can be provided in a low price with being a simple structure by accumulating vessels in a high density. As the vessel for measuring light and so on are accumulated in a cartridge container or a microplate, the process from beginning to end can be executed by only one container, and the process can efficiently and promptly be executed by reducing the necessity of the mechanical driving movement.
A seventh aspect of the present invention is that, in the sixth aspect, each vessel is formed to be elliptic in a horizontal section. As the container of this aspect of the invention is formed to be substantially elliptic, the flow of liquid becomes irregular when pipette tip discharges liquid, and the agitating efficiency can be improved by this aspect of the invention.
In this invention, a container may be comprised of a single vessel formed so as to be substantially concave in a vertical section. Or, a container may be comprised of a cartridge container or a microplate, in the main body of which plural vessels are arranged in a straight line or lines. It is preferable that a horizontal section of each vessel for storing liquid is formed so as to be elliptic.
An eighth aspect of the present invention is that, in the sixth or seventh aspect, vessels have various shapes or various capacities determined by a content of process. As the container can be constituted so as to be able to execute necessary treatment by only one container, the process can be completed efficiently and quickly.
A ninth aspect of the present invention is that, in the first to eighth aspect, the container is used for the process of liquid containing magnetic particles. For example, xe2x80x9cprocess for the liquid containing magnetic particlesxe2x80x9d is chemical luminousness inspection methods or EIA inspection methods such as the CLIA inspection method or the CLEIA inspection method and so on. Naturally, it is possible to use for the other inspection method, an extraction method, and a measurement method, too.
A tenth aspect of the present invention is that, in the first to ninth aspect, in each vessel, an antigen, an antibody, an enzyme or a DNA probe and so on is contained in the solid phase. Here, xe2x80x9cis contained in the solid phasexe2x80x9d means that an antigen and so on sticks to the inside wall of the container and so on in solid phase by coating and so on.
An eleventh aspect of the present invention is that, in the sixth to tenth aspect, the cartridge container has a base member, and plural vessels arranged along a line or lines in the base member, wherein the plural vessels comprise the necessary number of vessels for treatment, vessels for measuring light being able to couple with an optical measuring apparatus or an optical receiving unit in a light shielded state, or hole parts holding it, vessels accommodating or hole parts holding a pipette tip, tubes for PCR or hole parts holding it, or, vessels being contained in the solid phase or hole parts holding it, according to the process. Thus, the process from beginning to the optical measurement can be completed by only one container. Therefore, the necessity of the mechanical driving movement can be suppressed to the minimum. Also, the process can be promptly, reliably and collectively executed by reducing the distance and the time for the transfer of liquid and so on.
A twelfth aspect of the present invention is that, in the sixth to tenth aspect, the microplate has a base member, and plural vessels arranged in a matrix in the base member, wherein the plural vessels belonging to a group of vessels formed by dividing the matrix row-wise or column-wise comprises the necessary number of vessels for treatment, vessels for measuring light being able to couple with an optical measuring apparatus or an optical receiving unit in a light shielded state, or hole parts holding it, vessels accommodating or hole parts holding a pipette tip, tubes for PCR or hole parts holding it, or, vessels being contained in the solid phase or hole parts holding it, according to the process.
Here, xe2x80x9ca tube for PCR (polymerase chain reaction)xe2x80x9d is the tube whose shape is adapted to the equipment for the amplification of DNA. By this aspect of the invention, as the same process can be done at the same time by multi-nozzle for dispensing, process can be executed efficiently.
A thirteenth aspect of the present invention is that, in the eleventh or twelfth aspect, the vessel for measuring light comprises a measuring vessel shielded from external light and a hole part holding it dismountably, in the case the base member of the cartridge container or microplate is made of such a transmission material as a transparent material or a translucent material. In this invention, the measuring vessel has a light shielding characteristic can be made as a separate members from the microplate made of a material having a light transmitting characteristic. Consequently, manufacture of them as separate members can be more easier than that as one integral member, and the cost can be reduced.
A fourteenth aspect of the present invention is that, in the eleventh or twelfth aspect, the vessel for measuring light and the base member are formed as a unitary body in the case that the base member of the cartridge container or microplate is made of a light shielding material.
A fifteenth aspect of the present invention is that, in the eleventh to thirteenth aspect, the measuring vessel held in the vessel for measuring light has a coupling means to couple with an optical measuring apparatus or an optical receiving unit in a light shielded state, at the upper end of the meaning vessel, wherein the inside wall of the measuring vessel is formed so as to be of a high reflective rate by applying with white color and so on, and the outside of the measuring vessel is covered by a light shielding material. In order to be of xe2x80x9chigh reflective ratexe2x80x9d, it should be applied with white color, be made of white material, be applied with metallic color, or be made of a metal and so on. By this aspect of the invention, external light can be shielded, and light arisen by radiation can surely enter into an optical receiving unit and an optical measuring apparatus, and a reliable measuring can be executed.
A sixteenth aspect of the present invention is that, in the sixth to fifteenth aspect, the microplate or the cartridge container comprises a base member being formed so as to be substantially plate-like, plural vessels being arranged in a matrix or in a line in the base member, a wall-like leg part being projecting downwards at an edge of the base member so as to be lower than the outside bottom of the vessel in order to support the base member. By this aspect of the invention, as microplate and cartridge container can be made without distortion, they can be stably placed on a stage for the pipette device and so on.
A seventeenth aspect of the present invention is that, a container has a microplate or a cartridge container comprising a base member being formed so as to be substantially plate-like, plural vessels arranged in a matrix or in a line in the base member, and a partition or partitions with a fixed height being arranged along parallel to an edge of the base member or a boundary or boundaries separating between groups of vessels. By this aspect of the invention, cross contamination by mixing splashes from the other processing line and so on can be avoided efficiently
An eighteenth aspect of the present invention is that, in the sixth to seventeenth aspect, one of the vessels is formed so that the structure is adapted to a thermostatic means. For example, when a thermostatic means (for example, a thermostatic tank) which controls the temperature in a tank electrically is used, the tank should be formed so that the vessels can be contained in it.
In comparison with the treatment using only a single vessel, this invention can more efficiently and more completely facilitate the temperature of liquid to be kept at a predetermined temperature by transferring liquid from a liquid storage vessel to a vessel maintained at a predetermined temperature. In comparison with the case using only a single vessel, in which control of raising and lowering the temperature needs be executed by a heating means or transferring a container accompanied by liquid to a heating position, the reaction can more efficiently be executed by this aspect of the invention, and the amplification can be executed more easily and in a shorter time. And as the mechanism for transferring the container needs not be mounted, the structure of the equipment can be simplified. Furthermore, all process including the control of temperature, can be executed with one continuous operation by this aspect of the invention.
A nineteenth aspect of the present invention is that, in the eighteenth aspect, a lid body having a slit being able to be inserted by the pipette tip, is mounted so as to have a structure being adapted to a thermostatic means. By this aspect of the invention, the evaporation and cross contamination of liquid housed in a container can be efficiently avoided.
A twentieth aspect of the present invention is that, in the sixth to nineteenth aspect, a seal being able to be penetrated by the pipette tip, is attached by a heat deposition or a supersonic deposition to the upper surface of the base member of the cartridge container or the microplate in order to cover the opening of the each vessel.
Here, xe2x80x9ca seal being able to be penetrated by a pipette tipxe2x80x9d may be not only the tender thin film being easily penetrated, but also the tough one having a hole. The seal may be not only transparent, but also translucent or opaque, and may be made of aluminium foil or polyvinyl-chloride and so on. In order to execute a treatment in a container, the front end portion of the pipette tip needs penetrate the seal and be inserted into the container. By this aspect of the invention, the evaporation of liquid being contained in each vessel and the cross contamination, and the invasion by the miscellaneous germs from outside can be avoided. Therefore, the treatment with high reliability can be efficiently executed.
A twenty-first aspect of the present invention is that, a container has a microplate comprising plural cartridge containers in which the vessels are arranged in a row-wise or column-wise line and a binding part formed so as to be substantially like teeth of a comb having intervals between the cartridge containers being able to be inserted in by the partition and binding the end of each cartridge container, wherein the partitions are arranged so as to be substantially in parallel mutually at a fixed interval on the stage putting the microplate in order to partition the cartridge containers mutually. Here, the size of xe2x80x9ca fixed intervalxe2x80x9d needs be large enough for the cartridge containers of the microplate or each nozzle of multi-nozzle for dispensing to be capable of being separated between partitions one by one, with a certain space. The height of the partition is great enough to prevent from mixing a splash of liquid etc. arisen from pouring etc.. Instead of the partition, air curtains may be mounted between cartridge containers in order to prevent from mixing a splash of liquid etc.. As each neighboring cartridge container can be separated by a partition, mixture of substances other than target substances between the different cartridge containers (cross-contamination) can be efficiently avoided, and reliable treatment can be executed.
A twenty-second aspect of the present invention is that, in the twenty-first aspect, the binding part is formed so as to have such a strength as each cartridge container to be cut easily. By this aspect of the invention, as the binding part can be cut every cartridge container easily, only the necessary number of the cartridge containers can be cut off from the binding part and be used according to the content of the process, and therefore, cartridge container can be efficiently used without waste and efficiently.
Besides, in the twenty-first aspect of the invention and the present aspect of the invention, if the cartridge containers and the binding part are formed in a unitary body, the manufacture of the container can be simplified and the cost can be reduced. For example, xe2x80x9cto be cut easilyxe2x80x9d can be attained by forming the binding part to be thin.
A twenty-third aspect of the present invention is that, in the sixth to twenty-second aspect, the necessary number of the vessels of the cartridge container according to the process are arranged along a locus of a moving nozzle of the liquid sucking/discharging line, and the necessary number of the vessels of microplate according to each process are arranged in parallel along loci of moving nozzles of the liquid sucking/discharging lines.